A class of active ingredients having excellent analgesic effectiveness are substituted spirocyclic cyclohexane compounds which are inter alia known from WO 2004/043967 and WO 2008/040481.
Two particular compounds that are of great interest for use in the treatment of pain such as acute, visceral, neuropathic, cancer and chronic pain are (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4b]indol]-4-amine (in the following also referred to as (1r,4r)-1) and (1r,4r)-6′-fluoro-N-methyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4b]indol]-4-amine (in the following also referred to as (1r,4r)-2).
Substituted spirocyclic cyclohexane compounds such as (1r,4r)-1 and (1r,4r)-2 are conventionally prepared via a multi-step synthesis including an oxa-Pictet-Spengler reaction as one of the key steps as e.g. disclosed by WO 2004/043967.
The processes for the preparation of compounds (1r,4r)-1 and (1r,4r)-2 or physiologically acceptable acid addition salts thereof that are known so far are, however, not satisfactory in every respect and there is a demand for advantageous processes for the preparation of these compounds.
In particular, there is a demand for an alternative process that allows for controlling the diastereoselectivity of said process in a targeted manner, i.e. that allows for preparing (1r,4r)-1 and (1r,4r)-2 or physiologically acceptable acid addition salts thereof in pure diastereomeric form and, thus, suppressing at least partially the formation of undesired diastereomers.